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. 2024 Mar 26;32(4):250.
doi: 10.1007/s00520-024-08446-x.

Perturbations in inflammatory pathways are associated with shortness of breath profiles in oncology patients receiving chemotherapy

Affiliations

Perturbations in inflammatory pathways are associated with shortness of breath profiles in oncology patients receiving chemotherapy

Joosun Shin et al. Support Care Cancer. .

Abstract

Purpose: One plausible mechanistic hypothesis is the potential contribution of inflammatory mechanisms to shortness of breath. This study was aimed to evaluate for associations between the occurrence of shortness of breath and perturbations in inflammatory pathways.

Methods: Patients with cancer reported the occurrence of shortness of breath six times over two cycles of chemotherapy. Latent class analysis was used to identify subgroups of patients with distinct shortness of breath occurrence profiles (i.e., none (70.5%), decreasing (8.2%), increasing (7.8%), high (13.5%)). Using an extreme phenotype approach, whole transcriptome differential gene expression and pathway impact analyses were performed to evaluate for perturbed signaling pathways associated with shortness of breath between the none and high classes. Two independent samples (RNA-sequencing (n = 293) and microarray (n = 295) methodologies) were evaluated. Fisher's combined probability method was used to combine these results to obtain a global test of the null hypothesis. In addition, an unweighted knowledge network was created using the specific pathway maps to evaluate for interconnections among these pathways.

Results: Twenty-nine Kyoto Encyclopedia of Genes and Genomes inflammatory signaling pathways were perturbed. The mitogen-activated protein kinase signaling pathway node had the highest closeness, betweenness, and degree scores. In addition, five common respiratory disease-related pathways, that may share mechanisms with cancer-related shortness of breath, were perturbed.

Conclusions: Findings provide preliminary support for the hypothesis that inflammation contribute to the occurrence of shortness of breath in patients with cancer. In addition, the mechanisms that underlie shortness of breath in oncology patients may be similar to other respiratory diseases.

Keywords: Dyspnea; Gene expression; Inflammation; Neoplasms.

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Conflict of interest statement

Competing interests: Dr. Wong reported conflicts of interest outside of the submitted work: An immediate family member is an employee of Genentech with stock ownership and Dr. Wong receives royalties from UpToDate. The remaining authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
An undirected shortness of breath knowledge network generated from connections among the perturbed of inflammation-related Kyoto Encyclopaedia of Genes and Genomes (KEGG) signalling pathways associated with Shortness of Breath in Patients receiving chemotherapy. Nodes represent each of the KEGG signalling pathways. Edges represent connections between the pathways. Node size corresponds to betweenness centrality score (bigger is higher). Node fill shade corresponds to closeness centrality score (yellowish is higher). Node border colour represents KEGG Ontology classification (i.e., blue = signal transduction; red = immune system; grey = others). Abbreviations: ACTIN = regulation of actin cytoskeleton; APC = antigen processing and presentation; Apelin = apelin signalling pathway; APOP = apoptosis; CCC = complement and coagulation cascades; C-CR = cytokine-cytokine receptor interaction; C-DNA = cytosolic DNA-sensing pathway; Cell-Sene = cellular senescence; C-type LR = C-type lectin receptor signalling pathway; CXC = chemokine signalling pathway; ENDO = endocytosis; Fc-gamma = Fc gamma R-mediated phagocytosis; FoxO = FoxO signalling pathway; IgA = intestinal immune network for IgA production; JAK-STAT = JAK-STAT signalling pathway; MAPK = MAPK signalling pathway; NECROP = necroptosis; NET form = neutrophil extracellular trap formation; NF-kappa B = NF-kappa B signalling pathway; NK-cell = natural killer cell mediated cytotoxicity; NOD-LR = NOD-like receptor signalling pathway; PHAG = phagosome; PI3K-Akt = PI3K-Akt signalling pathway; PLT = platelet activation; RIG-I-IR = RIG-I-like receptor signalling pathway; Th17 cell = Th17 cell differentiation.

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